Project summary/abstract: Elucidating the mechanisms driving stage conversion in Toxoplasma gondii and Hammondia hammondi. Toxoplasma gondii is the world?s most common human parasitic infection. Although generally asymptomatic, T. gondii can result in severe disease in utero and in immunocompromised individuals, and this occurs due the presence of incurable cyst stages that can persist for the life of the host. T. gondii follows a facultative homoxenous/heteroxenous life cycle, allowing it to infect new and diverse intermediate hosts with orally infectious agents derived from both sexual (oocysts) and asexual reproduction (tissue cysts). This phenomenon is unique to T. gondii among other coccidian Apicomplexans, including its closest relative Hammondia hammondi. Despite extensive genomic similarity, H. hammondi is naturally avirulent and possesses dramatic phenotypic differences in both gene expression and life cycle progression. These differences suggest that despite possessing a similar genetic tool kit, H. hammondi and T. gondii differentially utilize their genetic components to progress through their distinct life stages. I have found these two parasites differentially develop tissue cysts and that tissue cyst formation in H. hammondi is not initiated by stressors known to mediate this process in T. gondii. Together, this data suggests that these two species utilize different mechanisms for stage progression. The goal of this proposal is to use this novel comparative system to identify parasite and host components uniquely driving stage progression in T. gondii.